There is a high incidence of chronic heavy alcohol use, which has known CNS toxicity, in populations at high risk for HIV infection. The main goal of this project is to determine the degree to which chronic alcohol use increases the CNS morbidity of HIV infection via a) direct effects, b) hastening the progression of the overall HIV disease process, or c) reducing treatment response. Our synergistic model of HIV infection and alcohol use predicts that the CNS morbidity in individuals who are HIV+ and chronic heavy alcohol users will be greater than the sum of that due to HIV infection or chronic alcohol use alone. Our goal will be achieved by using in vivo multi-slice proton magnetic resonance spectroscopic imaging (1 H MRSI) to measure the spatial and temporal patterns of brain neuron viability ( measured by N-acetylaspartate, a putative neuron maker) and gliosis (measured by choline-containing metabolites). We will measure brain region-specific /1H metabolite concentrations in four subject groups: 1) 120 HIV+ heavy chronic alcohol users, 2) 120 HIV+ light/non-drinkers, 3) 60 HIV-heavy chronic alcohol users, and 4) 60 HIV- light/non-drinkers. The two HIV+ samples will be matched for degree of systemic immunosuppression by CD4 percent, the two drinking samples will be matched on alcohol consumption. The specific aims of this cross-section and longitudinal study are to (1) determine whether chronic heavy alcohol using HIV-infected individuals have greater CNS morbidity than light/non- drinking HIV-infected individuals, (2) determine whether chronic heavy alcohol using HIV-infected individuals have a greater rate of progression of CNS morbidity and/or a lesser treatment response than light/non- drinking HIV-infected individuals have a greater rate of progression of CNS morbidity and/or a lesser treatment response than light/non-drinking HIV-infected individuals, (3) determine whether the effects of chronic heavy alcohol use and HIV infection on CNS morbidity and progression are additive or, as predicted by our synergistic model, exceed additive effects, and (4) test hypothesis both about the mechanisms underlying CNS metabolic abnormalities and about their impact on clinically important outcomes. Measurements of /1H metabolite concentrations are expected to facilitate early detection of brain involvement in HIV disease and alcohol abuse, possibly before structural brain changes and/or any definitive impairments are clinically evident, and they may predict the later development of structural changes and clinically significant impairments. This /1H MRSI could prove important in instituting aggressive interventions early in HIV CNS disease progression. By documenting neuronal and gliotic effects of chronic heavy alcohol use among HIV+ individuals, this project will help establish the magnitude of the public health problems posed by such use. It will also provide important information on whether and how chronic heavy alcohol use compromises the efficacy of anti-retroviral therapy.